Depressive disorder is a mood disorder or affective disorder caused by various reasons with depression as the main symptom, and is a group of clinical symptoms or states centering on depressive mood self-experience, which includes down mood in chief, incompatibility with circumstances and may vary from moodiness to inconsolability, or even occur a stupor. Severe ones may develop psychotic symptoms like hallucinations, delusions, etc. For some cases, anxiety and exercise-induced agitation are quite significant. Depressive disorder centers on depressive mood, thinking retardation and decline in volition, with various somatic symptoms present in most cases.
At present the antidepressants used in clinic primarily include the following kinds: the first generation classic antidepressants: including monoamine oxidase inhibitor (MAOI) such as isopropyl hydrazine, Moclobemide, etc., and the tricyclic antidepressants (TCA) such as Imipramine, Amitriptyline, Doxepin and Clomipramine, Maprotiline. The second generation antidepressants: These drugs include selective serotonin reuptake inhibitors and selective serotonin (SSRIs) and norepinephrine dual reuptake inhibitors such as Fluoxetine, Paroxetine, Citalopram, etc. As new drugs have developed rapidly, new drugs come out endlessly, for example venlafaxine, des-venlafaxine and vilazodone, etc. are sequently on sale, but currently selective serotonin reuptake inhibitors are still in chief. Such drugs are the most frequently and widely used in clinical application. The tricyclic antidepressants are the longest used in clinical application and the pharmacologic effects thereof are the most and fullest studied. In short, the main pharmacologic effects of antidepressants are: 1. blocking reuptake of monoamine neurotransmitters (mainly adrenaline (NA) and serotonin (5-HT)), increasing the amount of monoamine in neurosynaptic clefts thereby generating antidepressive effect. 2. Blocking various neurotransmitter receptors, which is unrelated to the therapeutic effect but is the main reason for many adverse reactions. For example blocking acetylcholine M receptor may lead to xerostomia, blurred vision, sinus tachycardia, constipation, urinary retention, glaucoma exacerbation and memory dysfunction, etc.; blocking adrenergic α1 receptors may lead to enhancement of the antihypertensive effect of prazosin, orthostatic hypotension, dizziness, reflex tachycardia; blocking histamine H1 receptors may lead to enhancement of central inhibitory effect, sedation, somnolence, weight gain and decreased blood pressure; blocking dopamine D2 receptors may lead to extrapyramidal symptoms and changes in endocrine, etc.
In “novel noradrenergic and specific serotoninergic antidepressant Mirtazapine, Jingping Zhao, Chinese Journal of Psychiatry, Vol. 35, No. 4”, disclosed is that as belonging to noradrenergic (NE) and specific 5-hydroxytryptaminergic (5HT) antidepressants (NaSSA), the unique pharmacological effect of mirtazapine is different from all the other antidepressants. Mirtazapine belongs to pyrazine-azepine compounds containing a tetracyclic structure, having levorotation, dextral 2 mirror isomers. The levorotatory form selectively blocks isoreceptors only, while the racemates can not only block isoreceptors but also block self-receptors, thus having most of the pharmacological activities. Demethylated mirtazapine is the only metabolite with pharmacological activity of mirtazapine, just occupying 3%-10% of the drug activity.
Although there are many options on antidepressants currently used in clinic, ideal drugs with desirable therapeutic effect are few. The effective rate of general clinical antidepressants is around 40%˜50%, and many antidepressants have serious or relatively serious side effects such as sexual dysfunction, weight gain and cardiovascular side effects. Additionally, for these antidepressants, particularly SSRIs, time (onset) of acting antidepressive effect is usually around 4-8 weeks. These serious side effects greatly affect the confidence of patients with depressive disorder in drug usage.
At present, new methods for treating and/or preventing depressive disorder are still expected in the art.